Effect of pretreatment with simvastatin on spinal cord ischemia-reperfusion injury in rats

Abstract

Objective: The aim of this study was to evaluate the pretreatment effect of simvastatin on spinal cord ischemia-reperfusion injury. Design: Prospective, interventional study. Setting: University research laboratory. Participants: Forty-five male Sprague-Dawley rats. Interventions: Rats were treated with oral simvastatin, 10 mg/kg (simvastatin group; n = 15) or saline (control group; n = 15) for 5 days before ischemia. Spinal cord ischemia was induced using a balloon-tipped catheter placed in the proximal descending aorta in the control and simvastatin groups, but not in the sham group (n = 15). Measurements and Main Results: Neurologic function was assessed daily using the motor deficit index until 7 days after reperfusion. After the last neurologic evaluation, a histologic examination of the spinal cord was performed. At day 1 after reperfusion, the simvastatin group showed a significantly lower motor deficit index compared with the control group (2.0, 2.0-2.0, v 4.0, 3.5-5.0; p < 0.001). This trend was sustained at day 7 (2.0, 1.5-2.0, v 4.0, 3.0-4.0; p < 0.001). The simvastatin group displayed a significantly larger number of normal motor neurons compared with the control group (mean ± SD, 31.7 ± 6.1 v 20.4 ± 4.4; p < 0.001). However, compared with the sham group, the simvastatin group displayed fewer intact motor neurons (sham group, 38.5 ± 5.1; p = 0.005). Conclusions: Pretreatment with simvastatin, 10 mg/kg, given orally for 5 days before the ischemia-reperfusion insult, improved the neurologic outcome and preserved more normal motor neurons compared with the control group in a rat model of spinal cord ischemia-reperfusion. © 2012 Elsevier Inc.